S187: UPDATED PHASE 1/2 DATA OF SAFETY AND EFFICACY OF CT103A, FULLY HUMAN BCMA-DIRECTED CAR T CELLS, IN RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: C. Li, D. Wang, Y. Song, J. Li, H Huang, B. Chen, J. Liu, K. Hu, H. Ren, X. Zhang, Z. Li, D. Zou, Q. Yin, L. Chen, Y. Hu, Y. Xu, Q. Cheng, Y. Guo, Y. Dong, L. Gao, S. Chen, A. Xu, S. Cai, M. Wu, J. Guo, Z. Yao, W. Wang, J. Wang, L. Chen, J. Zhou, L. Qiu
Journal: HemaSphere (2022)

Background: CT103A, a fully human BCMA-directed CAR-T therapy, showed excellent safety and promising efficacy in the ongoing phase 1/2 FUMANBA-1 study (ChiCTR1800018137, NCT05066646) in patients with relapsed/refractory multiple myeloma (Wang, ASH, 2021). Aims: We report updated data from the FUMANBA-1 study with more subjects and a longer duration of follow-up. Methods: Enrolled patients had received three or more prior lines of anti-myeloma therapy, including a proteasome inhibitor and an immunomodulatory agent, and were required to be refractory to the last line of therapy. CT103A was administered at RP2D of 1.0×106 CAR+ T cells/kg. Lymphodepletion with cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) was used for 3 consecutive days. Study objectives included safety and efficacy profile. Pharmacokinetics, pharmacodynamics, and immunogenicity were also explored. MRD in bone marrow aspirate was detected by EuroflowTM standardized flow cytometry with the sensitivity of 10-5. Adverse events (AEs) were graded using CTCAEv5.0, except that CRS and ICANS were graded by ASTCT criteria. Results: As of Jan 21, 2022, 79 patients received CT103A with the median follow-up of 9.6 months (range 1.2, 40.0). 28 (35.4%) patients had high-risk cytogenetic abnormality defined as del(17p), t(4;14), or t(14;16), and 11 (13.9%) had extramedullary plasmacytomas. Patients received a median of 5 (range 3, 23) prior lines of therapy. Notably, 13 (16.5%) had received prior non-human BCMA-targeted CAR-T cell therapy. ORR was 94.9% (75/79), with 55 (69.6%) patients achieving CR/sCR, and 71 (89.9%) achieving ≥VGPR. Median TTR was 16 days (range 11, 123), and the median time to CR/sCR was 95 days (range 14, 557). For 13 patients who had prior CAR-T therapy, ORR was 98.5%, with 6 (46.2%) achieving CR/sCR. For 11 patients with extramedullary disease at baseline, ORR was 100%, with 9 (81.8%) achieving CR/sCR. All patients with CR/sCR were MRD-negative. The median duration of MRD negativity was not reached. The probability of MRD negativity at month 12 was 88.7% (95% CI 65.9%, 96.6%). CRS occurred in 75 (94.9%) patients, of which only 2 (2.5%) had grade 3 CRS. The median time to onset of CRS was six days (range 1, 12) with a median duration of 5 days (range 2, 30). ICANS occurred in only 2 (2.5%) patients, of which one was grade 1, and the other was grade 2. All CRS were resolved, with the use of tocilizumab in 19 (25.3%) patients and steroids in 47 (62.7%). The most common ≥ grade 3 treatment-related AEs were hematological toxicities, including neutropenia (78.5%), leukopenia (74.7%), lymphopenia (55.7%), thrombocytopenia (54.4%), and anemia (46.8%). CT103A reached the peak at a median of 12 days (range 0, 26) after infusion and were still detectable in 40 of 61 evaluable patients (65.6%) at month 6 and 13 of 21 (61.9%) at month 12. Soluble BCMA decreased to the lower limit of quantification (LLOQ) at a median of 2 months and can maintain bellow LLOQ over 24 months. 11 (13.9%) patients were positive for anti-drug antibodies, of whom 1/76 (1.3%) developed anti-drug antibodies at month 3, 5/43 (11.6%) at month 6 and 5/16 (31.3%) at month 12. Among these, neutralizing antibodies were only identified in one patient (at month 12). Summary/Conclusion: Updated data from the Phase 1/2 FUMANBA-1 study continue to show encouraging efficacy of CT103A with a favorable safety profile in relapsed/refractory multiple myeloma. CT103A led to a deepening and durable response with robust expansion and prolonged persistence. Patients with prior BCMA CAR-T therapy could still benefit from CT103A.